Ladetto Marco, De Marco Federica, Benedetti Fabio, Vitolo Umberto, Patti Caterina, Rambaldi Alessandro, Pulsoni Alessandro, Musso Maurizio, Liberati Anna M, Olivieri Attilio, Gallamini Andrea, Pogliani Enrico, Rota Scalabrini Delia, Callea Vincenzo, Di Raimondo Francesco, Pavone Vincenzo, Tucci Alessandra, Cortelazzo Sergio, Levis Alessandro, Boccadoro Mario, Majolino Ignazio, Pileri Alessandro, Gianni Alessandro M, Passera Roberto, Corradini Paolo, Tarella Corrado
Divisione Universitaria di Ematologia, Cattedra di Ematologia, Torino, Italy.
Blood. 2008 Apr 15;111(8):4004-13. doi: 10.1182/blood-2007-10-116749. Epub 2008 Jan 31.
In this randomized multicenter study of 136 patients, 6 courses of CHOP (cyclo-phosphamide/doxorubicin/vincristine/prednisone) followed by rituximab (CHOP-R) were compared with rituximab-supplemented high-dose sequential chemotherapy with autografting (R-HDS) to assess the value of intensified chemo-therapy as a first-line treatment for high-risk follicular lymphoma (FL) after the introduction of monoclonal antibodies. The analysis was intention to treat with event-free survival (EFS) as the primary endpoint. Complete remission (CR) was 62% with CHOP-R and 85% with R-HDS (P < .001). At a median follow-up (MFU) of 51 months, the 4-year EFS was 28% and 61%, respectively (P < .001), with no difference in overall survival (OS). Molecular remission (MR) was achieved in 44% of CHOP-R and 80% of R-HDS patients (P < .001), and was the strongest independent outcome predictor. Patients relapsing after CHOP-R underwent salvage R-HDS in 71% of cases. Salvage R-HDS had an 85% CR rate and a 68% 3-year EFS (MFU, 30 months). We conclude that (1) achieving MR is critical for effective disease control, regardless of which treatment is used; (2) R-HDS ensures superior disease control and molecular outcome than CHOP-R, but no OS improvement; and (3) CHOP-R failures have a good outcome after salvage R-HDS, suggesting that relapsed/refractory FL could be the most appropriate setting for R-HDS-like treatments. This trial was registered at www.clinicaltrials.gov as no. NCT00435955.
在这项针对136例患者的随机多中心研究中，将6个疗程的CHOP（环磷酰胺/阿霉素/长春新碱/泼尼松）方案序贯利妥昔单抗（CHOP-R）与补充利妥昔单抗的大剂量序贯化疗联合自体移植（R-HDS）进行比较，以评估在引入单克隆抗体后强化化疗作为高危滤泡性淋巴瘤（FL）一线治疗的价值。分析采用意向性治疗，将无事件生存期（EFS）作为主要终点。CHOP-R方案的完全缓解（CR）率为62%，R-HDS方案为85%（P<0.001）。中位随访（MFU）51个月时，4年EFS分别为28%和61%（P<0.001），总生存期（OS）无差异。CHOP-R方案的患者中有44%实现分子缓解（MR），R-HDS方案为80%（P<0.001），且MR是最强的独立预后预测因素。CHOP-R方案治疗后复发的患者中，71%的病例接受了挽救性R-HDS治疗。挽救性R-HDS的CR率为85%，3年EFS为68%（MFU，30个月）。我们得出结论：（1）无论采用何种治疗方法，实现MR对有效控制疾病至关重要；（2）R-HDS比CHOP-R能确保更好的疾病控制和分子预后，但未改善OS；（3）CHOP-R治疗失败后接受挽救性R-HDS治疗的效果良好，这表明复发/难治性FL可能是类似R-HDS治疗的最合适情况。该试验已在www.clinicaltrials.gov上注册，注册号为NCT00435955。
